1.Study on therapy of leukemia through proliferated NK cell induced by low-dose radiation in nude mice
Yujia SHI ; Xiaosong PAN ; Yimin YAO ; Hong XU ; Qiu CHEN ; Haiyan LIU ; Haowen ZHANG ; Fenju LIU
Chinese Journal of Radiological Medicine and Protection 2011;31(1):17-20
Objective To separate NK cells of mice from NK cell separation medium and study inhibitory effect of proliferated NK cell induced by low dose radiation on the leukemia model of K562 cells.Methods Flow cytometry and 3H-TdR methods were respectively used to measure proliferation index and activity of NK cells treated with low-dose radiation( which means exposure dose in 20 cGy low LET beam or 5 cGy high LET beam).CD13 + cells were measured by flow cytometry and TNF-α content in blood-serum was detected by ELISA.In vivo,peripheral blood leucocyte count,index of liver,indexes of spleen and kidney were observed in control group and experimental group.Results The purity of NK cell separation was (82.54 ± 0.18)%.The proliferation index of NK cells at 24 hours after 80 mGy irradiated was 36.31 ± 1.32% ,(t =24.69,P <0.05).Killing activity of NK cell induced by low dose radiation to K562 cell was (12.59±0.63)%(t=6.63,P<0.05)and the inhibition ratio was 29.52%.Conclusion The injection of proliferated NK cell induced by low dose radiation demonstrated significant inhibitory effect on the growth of leukemia nude mouse.
2.Safety and efficacy of a treatment protocol in converting initially unresectable to resectable hepatocellular carcinoma
Ze ZHANG ; Yinbiao CAO ; Tao WAN ; Wenwen ZHANG ; Zhanbo WANG ; Junning CAO ; Bingyang HU ; Jun HAN ; Haowen TANG ; Liru PAN ; Shichun LU
Chinese Journal of Hepatobiliary Surgery 2022;28(1):15-20
Objective:To study the safety and efficacy of a treatment protocol using immune checkpoint inhibitors (ICIs) and antiangiogenic targeted drugs (AATDs) in converting 41 patients with initially unresectable to resectable hepatocellular carcinoma (HCC).Methods:The data of 41 patients with initially unresectable HCC treated with immunotherapy combined with targeted therapy from December 2018 to April 2021 in Chinese PLA General Hospital were analysed. There were 34 males and 7 females, aged (51.8±10.7) years. The clinical characteristics, conversion to resectable HCC, adverse drug reactions, surgical data and postoperative complications were analysed. Patients were followed-up by outpatients clinics or telephone calls.Results:There were 5 patients with Chinese Liver Cancer Staging (CNLC)-Ⅰb, 4 with CNLC-Ⅱ, 28 with CNLC-Ⅲa and 4 with CNLC-Ⅲb before the treatment protocol. Among them, 28 patients had portal vein tumor thrombosis (PVTT) and 4 had retroperitoneal lymph node metastases. All patients had a mean tumor diameter of (9.16±4.43) cm before and (6.49±4.69) cm after the treatment protocol. The latter was based on the last assessment before hepatectomy. The efficacy of the treatment protocol in converting unresectable to resectable HCC was assessed by the modified Response Evaluation Criteria in Solid Tumors after 3-15 cycles (median dose cycles, 5) of protocal therapy: 15 patients achieved a complete response; 15 patients achieved a partial response; 6 patients had a stable disease, and 5 patients had a progressive disease. 21 patients (51.2%) experienced adverse reactions associated with drug treatment, which resolved with symptomatic treatment or brief discontinuation of the therapy. All patients underwent successful hepatectomy. Postoperative complications of grade Ⅱ or higher occurred in 9 patients (22.0%). The cumulative overall survival rates at 6 months, 1 year and 2 years from diagnosis were 100.0%, 92.6% and 64.7% respectively. The cumulative overall survival rates at 6 months, 1 year and 2 years after surgery were 95.1%, 74.7% and 60.8%, and the recurrence-free survival rates at 6 months, 1 year and 2 years after surgery were 87.8%, 56.7% and 48.6%, respectively.Conclusions:This study provided preliminary evidences that surgical resection after immunotherapy combined with targeted therapy in patients with initially unresectable HCC was safe and efficacious.
3.Analysis of the risk factors related to prolonged drainage time in patients with selective abdominal drainage after laparoscopic cholecystectomy
Xinlan GE ; Haowen TANG ; Junning CAO ; Ke PAN ; Chonghui LI ; Bo LIU
Chinese Journal of Hepatobiliary Surgery 2022;28(4):280-283
Objective:To determine the risk factors of drainage time longer than 1 day in patients with selective abdominal drainage after laparoscopic cholecystectomy.Methods:The clinical data related to patients with selective abdominal drainage undergoing laparoscopic cholecystectomy from November 2009 to November 2019 at Chinese PLA General Hospital were retrospectively analyzed. Of 233 patients enrolled into this study, there were 147 males and 86 females, with a median aged 59.0 (47.5, 65.5) years old. The patients were divided into drainage time 1 day group of 65 patients and longer than 1 day group of 168 patients according to postoperative drainage time. The baseline data and perioperative data were collected, the risk factors correlated with drainage time longer than 1 day were analyzed.Results:The drainage time was 1 in the 1 day group and 2~8 in another group. Among the 233 patients, there was one with biliary leakage and 14 patients had abdominal bleeding, all of them healed after 2~3 days. All of the 233 patients were recovered when discharged. Independent risk factors related to drainage time longer than 1 day include BMI≥28 kg/m 2 ( OR=3.443, 95% CI: 1.411-8.405, P=0.007), operation time ≥65 min ( OR=2.570, 95% CI: 1.310-5.045, P=0.006), thickness of gallbladder wall ≥0.5 cm ( OR=12.720, 95% CI: 1.350-5.478, P=0.005), postoperative stomachache ( OR=13.537, 95% CI: 1.685-108.748, P=0.014) and postoperative fever ( OR=8.156, 95% CI: 1.035-64.249, P=0.046). Conclusion:For patients undergoing selective abdominal drainage after laparoscopic cholecystectomy with BMI ≥28 kg/m 2, operation time ≥65 min, gallbladder wall thickness ≥0.5 cm, postoperative abdominal pain and fever, clinicians should appropriately prolong the drainage time to ensure medical safety.
4.Analysis of goitrogenic effect of goitrogen in food
Haowen PAN ; Honglei XIE ; Xin HOU ; Meng ZHAO ; Wenjing CHE ; Jia LI ; Yue SU ; Lanchun LIU ; Zexu ZHANG ; Zongyu YUE ; Peng LIU
Chinese Journal of Endemiology 2024;43(1):77-81
Goiter is a kind of non-inflammatory and non-neoplastic hyperplasia and enlargement. Many studies have shown that substances such as thiocyanates and isothiocyanates can prevent the development of a variety of tumors. However, some studies have also found that such substances can lead to goiter. In this article, relevant information on common goitrogen in food are collected to explore their mechanism of action, laying a foundation for guiding residents to maintain a healthy and balanced diet.
5.Costunolide covalently targets NACHT domain of NLRP3 to inhibit inflammasome activation and alleviate NLRP3-driven inflammatory diseases.
Haowen XU ; Jiahao CHEN ; Pan CHEN ; Weifeng LI ; Jingjing SHAO ; Shanshan HONG ; Yi WANG ; Lingfeng CHEN ; Wu LUO ; Guang LIANG
Acta Pharmaceutica Sinica B 2023;13(2):678-693
The NLRP3 inflammasome's core and most specific protein, NLRP3, has a variety of functions in inflammation-driven diseases. Costunolide (COS) is the major active ingredient of the traditional Chinese medicinal herb Saussurea lappa and has anti-inflammatory activity, but the principal mechanism and molecular target of COS remain unclear. Here, we show that COS covalently binds to cysteine 598 in NACHT domain of NLRP3, altering the ATPase activity and assembly of NLRP3 inflammasome. We declare COS's great anti-inflammasome efficacy in macrophages and disease models of gouty arthritis and ulcerative colitis via inhibiting NLRP3 inflammasome activation. We also reveal that the α-methylene-γ-butyrolactone motif in sesquiterpene lactone is the certain active group in inhibiting NLRP3 activation. Taken together, NLRP3 is identified as a direct target of COS for its anti-inflammasome activity. COS, especially the α-methylene-γ-butyrolactone motif in COS structure, might be used to design and produce novel NLRP3 inhibitors as a lead compound.